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Mutant prion protein D202N associated with familial prion disease is retained in the endoplasmic reticulum and forms 'curly' intracellular aggregates.
- Source :
-
Journal of molecular neuroscience : MN [J Mol Neurosci] 2007; Vol. 32 (1), pp. 90-6. - Publication Year :
- 2007
-
Abstract
- Transmissible Spongiform Encephalopathies are fatal neurodegenerative disorders of humans and animals that are familial, sporadic, and infectious in nature. Familial disorders of humans include Gerstmann-Straussler-Scheinker disease (GSS), familial Creutzfeldt-Jakob disease (CJD), and fatal familial insomnia, and result from point mutations in the prion protein gene. Although neurotoxicity in familial cases is believed to result from a spontaneous change in conformation of mutant prion protein (PrP) to the pathogenic PrP-scrapie (PrPSc) form, emerging evidence indicates otherwise. We have investigated the processing and metabolism of mutant PrP D202N (PrP202N) in cell models to elucidate possible mechanisms of cytotoxicity. In this report, we demonstrate that PrP202N expressed in human neuroblastoma cells fails to achieve a mature conformation following synthesis and accumulates in the endoplasmic reticulum as 'curly' aggregates. In addition, PrP202N cells show increased sensitivity to free radicals, indicating that neuronal susceptibility to oxidative damage may account for the neurotoxicity observed in cases of GSS resulting from PrP D202N mutation.
- Subjects :
- Cell Line, Tumor
Detergents
Endoplasmic Reticulum pathology
Free Radicals metabolism
Humans
Mutation
Neuroblastoma
Oxidative Stress physiology
Prion Diseases genetics
Prions chemistry
Protein Folding
Solubility
Endoplasmic Reticulum metabolism
Prion Diseases metabolism
Prion Diseases pathology
Prions genetics
Prions metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0895-8696
- Volume :
- 32
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of molecular neuroscience : MN
- Publication Type :
- Academic Journal
- Accession number :
- 17873292
- Full Text :
- https://doi.org/10.1007/s12031-007-0023-6